Cleistanthin A (I) is a diphyllin glycoside isolated from the tropical plant Cleistanthus collinus:

Cleistanthin A is a diphyllin glycoside having anticancer potential. It is found to arrest growth by inhibiting DNA synthesis and cancer cell division and by driving cancer cells to apoptosis. These properties of cleistanthin A renders it promising agent useful in regimens for treating. The conventional process for the isolation of cleistanthin A comprises the steps of treating the dried leaves of Cleistanthus collinus with petroleum ether to obtain a defatted powder, which is subsequently extracted with acetone and treated with benzene and chloroform to afford a black residue. Pure cleistanthin A is then isolated following recrystallization with acetone. Because such a process is lengthy and not sufficient for gram scale quantities, synthetic procedures have been developed which culminate in the glycosylation of diphyllin (II):

Diphyllin (II) is thus a key intermediate in the synthesis of cleistanthin A. The synthesis of diphyllin is reported in WO 2010/089778, the entirety of which is herein incorporated by reference. This synthesis, while accomplished in only five linear steps from commercially available starting material, includes a metallation step requiring extremely low temperatures. Such temperatures, while may be easy to carry out on small laboratory scale, are exponentially problematic on a commercial scale, requiring the use of hazardous reagents and long reaction times. Further, such conditions limit the scale on which a compound can be manufactured, ultimately increasing the production cost of the active pharmaceutical ingredient (API). Hence, there remains a need for a more robust, of shorter duration and commercially viable synthesis of diphyllin, its analogs and intermediates thereof.